Endomorphins are natural opioid neurotransmitters central to pain relief. The two known endomorphins, endomorphin-1 and endomorphin-2, are tetrapeptides, consisting of Tyr-Pro-Trp-Phe and Tyr-Pro-Phe-Phe amino acid sequences respectively. These sequences fold into tertiary structures with high specificity and affinity for the μ-opioid receptor, binding it exclusively and strongly. Bound μ-opioid receptors typically induce inhibitory effects on neuronal activity. Endomorphins exist within the central and peripheral nervous systems, where endomorphin-1 is concentrated in the brain and upper brainstem, and endomorphin-2 is concentrated in the spinal cord and lower brainstem. As the major ligand of the μ-opioid receptor, which is the target receptor of morphine and its derivatives, endomorphins possess significant potential as analgesics with reduced side effects and risk of addiction.